Metronidazole
P01A - Agents against amoebiasis and other protozoal diseases
ATC P01AB01
Small molecule
approved 1963
Oral
Parenteral
Topical
Natural product
Black-box warning
JFDA label: Flanizol 250
⚠ Black-Box Warning
- carcinogenicity — ChEMBL drug_warning (Black Box Warning) | United States
- infectious disease — ChEMBL drug_warning (Black Box Warning) | United States
- nephrotoxicity — ChEMBL drug_warning (Black Box Warning) | United States
- Metronidazole has been shown to be carcinogenic in mice and rats (see PRECAUTIONS ). Unnecessary use of the drug should be avoided. Its use should be reserved for the conditions described in the INDIC
Mechanism of Action
Inhibitor of DNA — DNA inhibitor
| Target | Action | Gene / class |
|---|---|---|
| DNA efficacy | INHIBITOR |
Indications
Approved
- Amebiasis — amebiasis
- Bacterial Infections — bacterial disease
- Duodenal Ulcer — duodenal ulcer
- Infections — infection
- Intraabdominal Infections — infection
- Pneumonia — pneumonia
- Rosacea — rosacea
- Sepsis — Sepsis
- Trichomonas Infections — trichomoniasis
- Uterine Cervicitis — endocervicitis
- Vaginosis, Bacterial — bacterial vaginosis
Off-label
- Abscess
- Appendicitis
- Blepharitis
- Brain Diseases
- Candidiasis
- Carcinoma, Non-Small-Cell Lung
- Clostridium Infections
- Colitis, Ulcerative
- Colorectal Neoplasms
- Crohn Disease
- Diarrhea
- Enterocolitis, Pseudomembranous
- Fecal Incontinence
- Giardiasis
- Gingivitis
- HIV Infections
- Helicobacter Infections
- Hemorrhoids
- Hidradenitis Suppurativa
- Leukemia, Lymphocytic, Chronic, B-Cell
- Lichen Planus, Oral
- Lymphoma, Non-Hodgkin
- Malnutrition
- Mycoses
- Pain
- Pancreatic Neoplasms
- Pelvic Inflammatory Disease
- Periodontal Diseases
- Periodontitis
- Pilonidal Sinus
- Rectal Neoplasms
- Skin Diseases
- Trichomonas Vaginitis
- Tuberculosis
- Tuberculosis, Multidrug-Resistant
- Uterine Cervical Neoplasms
- Vaginal Discharge
- Vaginitis
Antimicrobial Spectrum
Expected / intrinsic spectrum (EUCAST breakpoints & labels) — not local resistance. Source: EUCAST v16 · openfda-label.
Bacteria
| Organism | Activity | MIC |
|---|---|---|
| Anaerobes | Susceptible | 4.0 mg/L |
| Helicobacter pylori | Susceptible | 8.0 mg/L |
Protozoa
| Organism | Activity | MIC |
|---|---|---|
| Bacteroides fragilis | Active | — |
| Bacteroides thetaiotaomicron | Active | — |
| Entamoeba histolytica | Active | — |
| Trichomonas vaginalis | Active | — |
Contraindications
Source: Curated · openFDA
- Concurrent alcohol ingestion or within 48 h of use (disulfiram-like reaction) Absolute
- First trimester of pregnancy (relative CI — teratogenicity in animal studies) Absolute
- Hypersensitivity Metronidazole tablet are contraindicated in patients with a prior history of hypersensitivity to metronidazole or other nitroimidazole derivatives. In patients with trichomoniasis, metronidazole tablet are contraindicated during the first trimester of pregnancy (see PRECAUTIONS ). Psychotic Reaction with Disulfiram Use of oral metronidazole is associated with psychotic reactions in alcoholic patients who were using disulfiram concurrently. Do not administer metronidazole to patients who have taken disulfiram within the last two weeks (see PRECAUTIONS, Drug Interactions ). Interaction with Alcohol Use of oral metronidazole is associated with a disulfiram-like reaction to alcohol, including abdominal cramps, nausea, vomiting, headaches, and flushing. Discontinue consumption of alcohol or products containing propylene glycol during and for at least three days after therapy with metronidazole (see PRECAUTIONS, Drug Interactions ). Cockayne Syndrome Metronidazole Tablets are contraindicated in patients with Cockayne syndrome. Severe irreversible hepatotoxicity/acute liver failure with fatal outcomes have been reported after initiation of metronidazole in patients with Cockayne syndrome (see ADVERSE REACTIONS ). Absolute
Adverse Reactions
Very Common >10%Common 1–10%Uncommon 0.1–1%
Rare 0.01–0.1%Very Rare <0.01%Not Known
Nervous system disorders (4)
Common Dizziness · Headache
Uncommon Peripheral neuropathy (prolonged use)
Rare CNS toxicity (high-dose IV)
Renal and urinary disorders (1)
Common Dark urine
Immune system disorders (1)
Common Disulfiram-like reaction with alcohol
Gastrointestinal disorders (2)
Very Common Metallic taste · Nausea
Dosing
Source: openFDA
Trichomoniasis: In the Female: One-day treatment − two grams of metronidazole tablets, given either as a single dose or in two divided doses of one gram each, given in the same day. Seven-day course of treatment − 250 mg three times daily for seven consecutive days. There is some indication from controlled comparative studies that cure rates as determined by vaginal smears and signs and symptoms, may be higher after a seven-day course of treatment than after a one-day treatment regimen. The dosage regimen should be individualized. Single-dose treatment can assure compliance, especially if administered under supervision, in those patients who cannot be relied on to continue the seven-day regimen. A seven-day course of treatment may minimize reinfection by protecting the patient long enough for the sexual contacts to obtain appropriate treatment. Further, some patients may tolerate one treatment regimen better than the other. Pregnant patients should not be treated during the first trimester (see CONTRAINDICATIONS ). In pregnant patients for whom alternative treatment has been inadequate, the one-day course of therapy should not be used, as it results in higher serum levels which can reach the fetal circulation (see PRECAUTIONS, Pregnancy ). When repeat courses of the drug are required, it is recommended that an interval of four to six weeks elapse between courses and that the presence of the trichomonad be reconfirmed by appropriate laboratory measures. Total and differential leukocyte counts should be made before and after re-treatment. In the Male: Treatment should be individualized as it is for the female. Amebiasis Adults: For acute intestinal amebiasis (acute amebic dysentery): 750 mg orally three times daily for 5 to 10 days. For amebic liver abscess: 500 mg or 750 mg orally three times daily for 5 to 10 days. Pediatric patients : 35 to 50 mg/kg/24 hours, divided into three doses, orally for 10 days. Anaerobic Bacterial Infections In the treatment of most serious anaerobic infections, intravenous metronidazole is usually administered initially. The usual adult oral dosage is 7.5 mg/kg every six hours (approx. 500 mg for a 70-kg adult). A maximum of 4 g should not be exceeded during a 24-hour period. The usual duration of therapy is 7 to 10 days; however, infections of the bone and joint, lower respiratory tract, and endocardium may require longer treatment. Dosage Adjustments Patients with Severe Hepatic Impairment For patients with severe hepatic impairment (Child-Pugh C), the dose of metronidazole tablets should be reduced by 50% (see CLINICAL PHARMACOLOGY and PRECAUTIONS ). Patients Undergoing Hemodialysis: Hemodialysis removes significant amounts of metronidazole and its metabolites from systemic circulation. The clearance of metronidazole will depend on the type of dialysis membrane used, the duration of the dialysis session, and other factors. If the administration of metronidazole cannot be separated from the hemodialysis session, supplementation of metronidazole dosage following the hemodialysis session should be considered, depending on the patient's clinical situation (see CLINICAL PHARMACOLOGY ).
Warnings & Precautions
Source: openFDA
Boxed Warning
Metronidazole has been shown to be carcinogenic in mice and rats (see PRECAUTIONS ). Unnecessary use of the drug should be avoided. Its use should be reserved for the conditions described in the INDICATIONS AND USAGE section below.
Warnings & Precautions
Hypersensitivity Reactions Hypersensitivity reactions including severe cutaneous adverse reactions (SCARs) can be serious and potentially life threatening (see ADVERSE REACTIONS ). Severe Cutaneous Adverse Reactions Severe cutaneous adverse reactions (SCARs) including toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) have been reported with the use of metronidazole. Symptoms can be serious and potentially life threatening (If symptoms or signs of SCARs develop, discontinue metronidazole tablets immediately and institute appropriate therapy. Central and Peripheral Nervous System Effects Encephalopathy and peripheral neuropathy: Cases of encephalopathy and peripheral neuropathy (including optic neuropathy) have been reported with metronidazole. Encephalopathy has been reported in association with cerebellar toxicity characterized by ataxia, dizziness, and dysarthria. CNS lesions seen on MRI have been described in reports of encephalopathy. CNS symptoms are generally reversible within days to weeks upon discontinuation of metronidazole. CNS lesions seen on MRI have also been described as reversible. Peripheral neuropathy, mainly of sensory type has been reported and is characterized by numbness or paresthesia of an extremity. Convulsive seizures have been reported in patients treated with metronidazole. Aseptic meningitis: Cases of aseptic meningitis have been reported with metronidazole. Symptoms can occur within hours of dose administration and generally resolve after metronidazole therapy is discontinued. The appearance of abnormal neurologic signs and symptoms demands the prompt evaluation of the benefit/risk ratio of the continuation of therapy (see ADVERSE REACTIONS ).
Pregnancy & Lactation
Pregnancy
FDA category B
Safe
Safe in all trimesters at standard doses. First-line for bacterial vaginosis (associated with preterm birth when untreated). IV use for serious anaerobic infections acceptable
Lactation
Caution
Hale L3
Opinions vary among experts on the advisability of using metronidazole during longer-term therapy while breastfeeding, but so
Chemistry & Properties
| Formula | C6H9N3O3 |
|---|---|
| Molecular weight | 171.16 g/mol |
| IUPAC name | 2-(2-methyl-5-nitroimidazol-1-yl)ethanol |
| CAS | 443-48-1 |
| PubChem CID | 4173 |
| InChIKey | VAOCPAMSLUNLGC-UHFFFAOYSA-N |
| logP | 0.09 (XLogP 0.0) |
| Polar surface area | 81.19 Ų |
| H-bond acceptors / donors | 5 / 1 |
| Drug-likeness (QED) | 0.52 |
| Lipinski violations | 0 |
SMILES
Cc1ncc([N+](=O)[O-])n1CCOBiology & Pharmacokinetics
Pharmacokinetics predicted
| Bioavailability | 10.0% |
|---|---|
| Half-life | 2.749 h |
| Volume of distribution | 0.898 L/kg |
| Protein binding | 17.4% |
| BBB penetrant | Yes |
Enzyme interactions
| Enzyme | Role | Detail |
|---|---|---|
| CYP2C19 | Substrate | — |
| CYP2C9 | Substrate | — |
| CYP3A4 | Substrate | — |
Transporters
BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MATE1 (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)MRP3 (Inhibitor)MRP4 (Inhibitor)NTCP (Inhibitor)OAT3 (Inhibitor)OATP1B1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)
Drug–drug interactions (100+, DDInter)
| Interacting drug | Severity | Management |
|---|---|---|
| Amprenavir | major | |
| Anisindione | major | |
| Busulfan | major | |
| Dicoumarol | major | |
| Disulfiram | major | |
| Ethanol | major | |
| Typhoid vaccine (live) | major | |
| Vibrio cholerae CVD 103-HgR strain live antigen (live) | major | |
| Warfarin | major | |
| Adalimumab | moderate | |
| Amiodarone | moderate | |
| Amobarbital | moderate | |
| Atorvastatin | moderate | |
| Auranofin | moderate | |
| Aurothioglucose | moderate | |
| Benznidazole | moderate | |
| Bifidobacterium longum infantis | moderate | |
| Bortezomib | moderate | |
| Bosentan | moderate | |
| Brentuximab vedotin | moderate | |
| Butabarbital | moderate | |
| Butalbital | moderate | |
| Cabazitaxel | moderate | |
| Capecitabine | moderate | |
| Carbamazepine | moderate | |
| Carboplatin | moderate | |
| Carfilzomib | moderate | |
| Celecoxib | moderate | |
| Cerivastatin | moderate | |
| Certolizumab pegol | moderate | |
| Chloramphenicol | moderate | |
| Chloroquine | moderate | |
| Cholestyramine | moderate | |
| Cisplatin | moderate | |
| Colchicine | moderate | |
| Crizotinib | moderate | |
| Cyclophosphamide | moderate | |
| Cyclosporine | moderate | |
| Dapsone | moderate | |
| Didanosine | moderate |
Showing 40 of 100+.
Registered Products (56)
| Brand | Form / strength | Pack | Agent | Citizen (JOD) |
|---|---|---|---|---|
| Ramazol | Tablet 250 mg | 20 tab pack varies | AL-RAM PHARMA.INDUS.CO.LTD/JORDAN | 0.610 |
| Metrazin Cap | Capsule 375 mg | 10 cap | MIDDLE EAST PHARMA&CHEMICAL IND/JORDAN | 0.830 |
| Ramazol | Tablet 500 mg | 20 tab pack varies | AL-RAM PHARMA.INDUS.CO.LTD/JORDAN | 1.000 |
| Metrozole | Tablet 250 mg | 20 tab pack varies | THE JORDANIAN PHARMACEUTICAL MANUFACTURING COMPANY/JORDAN | 1.030 |
| Metrozole suspension | Suspension 125 mg/5 ml | 100 ml | THE JORDANIAN PHARMACEUTICAL MANUFACTURING COMPANY/JORDAN | 1.080 |
| Nidazole 125 Suspension | Suspension 125 mg/5 ml | 100 ml | Hikma Pharmaceuticals Co.Ltd/Jordan | 1.170 |
| Flanizol Tablet | Tablet 250 mg | 30 tab pack varies | UNITED PHARM.MFG.CO.LTD(UPM)/JORDAN | 1.240 |
| Nidazole 250 Tablets | Tablet 250 mg | 30 tab pack varies | Hikma Pharmaceuticals Co.Ltd/Jordan | 1.240 |
| Ramazol | Tablet 250 mg | 30 tab pack varies | AL-RAM PHARMA.INDUS.CO.LTD/JORDAN | 1.240 |
| Protozol Suspension | Suspension 125 mg/5 ml | 100 ml pack varies | The Arab Pharmaceutical Manufacturing PSC/Salt | 1.250 |
| Flanizol 500 Tablets | Tablet 500 mg | 20 tab pack varies | UNITED PHARM.MFG.CO.LTD(UPM)/JORDAN | 1.300 |
| Metrozole | Tablet 500 mg | 20 tab | THE JORDANIAN PHARMACEUTICAL MANUFACTURING COMPANY/JORDAN | 1.300 |
| Dumozol 250Tabs | Tablet 250 mg | 24 tab | Reda Jardaneh Drug Store | 1.380 |
| Joswe Metro | Tablet 250 mg | 20 tab | JORDAN SWEDEN MEDICAL&STERILE.CO(JOSWE)/JORDAN | 1.380 |
| Flagyl Oral Tabs | Tablet 250 mg | 20 tab | Ulfa Pharma Co. | 1.410 |
| Metrolag Tab | Tablet 250 mg | 20 tab | Reda Jardaneh Drug Store | 1.490 |
| metrazin vaginal ovules | Vaginal 500 mg | 10 | MIDDLE EAST PHARMA&CHEMICAL IND/JORDAN | 1.560 |
| Nidazole 200 Suspension | Suspension 200 mg/5 ml | 100 ml | Hikma Pharmaceuticals Co.Ltd/Jordan | 1.720 |
| Metroza Cream | Cream 1 % | 15 g tube | PHILADELPHIA PHAEMACEUTICALS.COMP/JORDAN | 1.800 |
| Metroza Gel | Gel 0.75 % | 15 g tube | PHILADELPHIA PHAEMACEUTICALS.COMP/JORDAN | 1.800 |
| Flanizol 500 Tablets | Tablet 500 mg | 30 tab pack varies | UNITED PHARM.MFG.CO.LTD(UPM)/JORDAN | 1.950 |
| Nidazole 500 Tablets | Tablet 500 mg | 30 tab pack varies | Hikma Pharmaceuticals Co.Ltd/Jordan | 1.950 |
| Ramazol | Tablet 500 mg | 30 tab pack varies | AL-RAM PHARMA.INDUS.CO.LTD/JORDAN | 1.950 |
| Flagyl Vag Ovules | Vaginal 0.5 g | 10 Ovules | Ulfa Pharma Co. | 2.100 |
| Rosametra Gel | Gel 0.75 g/100GM | 30 GM/1 TUB | Sukhtian Pharma Co. (SP) | 2.260 |
| Flagyl Suspension | Suspension 125 mg/5 ml | 120 ml | Ulfa Pharma Co. | 2.280 |
| Flagyl Tabs | Tablet 500 mg | 14 tab | Ulfa Pharma Co. | 2.460 |
| NewFlageed | Vaginal 0.5 g | 10 Ovules | Al-Gadeed Pharmaceutical Industries/JORDAN | 2.510 |
| Joswe Metro Forte | Tablet 500 mg | 24 tab pack varies | JORDAN SWEDEN MEDICAL&STERILE.CO(JOSWE)/JORDAN | 2.720 |
| Dentagyl Tablet | Tablet 125 mg, 750.000 IU | 20 tab | The Arab Pharmaceutical Manufacturing PSC/Salt | 3.320 |
| Oragin Tablets | Tablet 125 mg, 750000 IU | 20 tab pack varies | THE JORDANIAN PHARMACEUTICAL MANUFACTURING COMPANY/JORDAN | 3.320 |
| Joswe Metro Forte | Tablet 500 mg | 30 tab pack varies | JORDAN SWEDEN MEDICAL&STERILE.CO(JOSWE)/JORDAN | 3.400 |
| Metrolag Tab | Tablet 500 mg | 24 tab | Reda Jardaneh Drug Store | 3.700 |
| Protozol-D Tablets | Tablet 250 mg, 300 mg | 3x10's | The Arab Pharmaceutical Manufactruing Co. | 3.700 |
| Nidazole 250 Tablets | Tablet 250 mg | 500 tab pack varies | Hikma Pharmaceuticals Co.Ltd/Jordan | 10.030 |
| Nidazole 250 Tablets | Tablet 250 mg | 1000 tab pack varies | Hikma Pharmaceuticals Co.Ltd/Jordan | 24.530 |
| Ramazol | Tablet 250 mg | 1000 tab pack varies | AL-RAM PHARMA.INDUS.CO.LTD/JORDAN | 27.450 |
| Metrozole | Tablet 250 mg | 1000 tab pack varies | THE JORDANIAN PHARMACEUTICAL MANUFACTURING COMPANY/JORDAN | 28.880 |
| Flanizol 250 | Tablet 250 mg | 1000 tab pack varies | UNITED PHARM.MFG.CO.LTD(UPM)/JORDAN | 33.060 |
| Ramazol | Tablet 500 mg | 1000 tab pack varies | AL-RAM PHARMA.INDUS.CO.LTD/JORDAN | 45.000 |
| Protozol Suspension | Suspension 125 mg/5 ml | 50 Bottle X 100mlÙستÙÙÙ ÙÙ 25 عبÙØ© ض٠٠Øز٠ة (Shrink) pack varies | The Arab Pharmaceutical Manufacturing PSC/Salt | 45.900 |
| Nidazole 500 Tablets | Tablet 500 mg | 1000 tab pack varies | Hikma Pharmaceuticals Co.Ltd/Jordan | 52.000 |
| Flanizol 500 Tablets | Tablet 500 mg | 1000 tab pack varies | UNITED PHARM.MFG.CO.LTD(UPM)/JORDAN | 52.040 |
| Oragin Tablets | Tablet 125 mg, 750000 IU | 660 tab pack varies | THE JORDANIAN PHARMACEUTICAL MANUFACTURING COMPANY/JORDAN | 93.130 |
| Colpocin-T | Injection 5 mg/ml | 100 ml | Al Hilal Drug Store | — |
| EFLARON SOL/IV INF | Solution 5 mg/1 ml | 100 ml | Reda Jardaneh Drug Store | — |
| Fungizol | Solution 500 mg/100 ml | 500 mg | MS-pharma jordan | — |
| Fungizol 5mg/1ml Solution For Infusion | Infusion 5 mg/ml | 1 vial pack varies | MS PHARMA/JORDAN | — |
| Fungizol 5mg/1ml Solution For Infusion | Infusion 5 mg/ml | 10 vial pack varies | MS PHARMA/JORDAN | — |
| METRONIDAZOLE I.V Braun | Solution 500 mg/100 ml | 100 ml | THE ARAB DRUG STORE P.S.C | — |
| METRONIDAZOLE IV INFUSION G.B. | Infusion 0.5 % | 100 ml pack varies | Sabbagh Drug Store | — |
| METRONIDAZOLE IV INFUSION G.B. | Infusion 0.5 % | 100 ml pack varies | Sabbagh Drug Store | — |
| Metrogyl Injection | Powder for Injection 500 mg | 100 ml | Roya Tholathiyat Al Abaad Drug Store | — |
| Metronidazole Fresenius 500mg/100ml Solution for Infusion | Infusion 500 mg/100 ml | 100 ml | Sun Set Drug Store | — |
| POLGYL 0.5% Solution for I.V. Perfusion | Solution 500 mg/100 ml | 100 ml | JAWEDA INT. DRUD STORE | — |
| Supplin Infusion | Infusion 500 mg | 100 ml | Nabulsi Drug Store | — |